MRI‐Visible siRNA Nanomedicine Directing Neuronal Differentiation of Neural Stem Cells in Stroke

Abstract

A major challenge in stroke treatment is the restoration of neural circuit in which neuron function plays a central role. Although transplantation of exogenous neural stem cells (NSCs) is admittedly a promising therapeutical means, the treatment outcome is greatly affected due to the poor NSCs differentiation into neurons caused by myelin associated inhibitory factors binding to Nogo-66 receptor (NgR). Herein, a nanoscale polymersome is developed to codeliver superparamagnetic iron oxide nanoparticles and siRNA targeting NgR gene (siNgR) into NSCs. This multifunctional nanomedicine directs neuronal differentiation of NSCs through silencing the NgR gene and meanwhile allows a noninvasive monitoring of NSC migration with magnetic resonance imaging. An improved recovery of neural function is achieved in rat ischemic stroke model. The results demonstrate the great potential of the multifunctional siRNA nanomedicine in stroke treatment based on stem cell transplantation.

Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy

“…NSC-based therapy is expected to offer unique therapeutic benefits to stroke, through differentiation into neurons to remedy damaged neurons and thereby reconstruct injured functional neural circuitry. , To our knowledge, this nanomedicine was the first one ever developed to direct neuronal stem cell differentiation via lncRNA downregulation. Previously, we have successfully used intracellular delivery of the siRNA targeting Nogo-66 receptor (NgR) to direct neuronal differentiation of NSCs through silencing the NgR gene . In the present study, we used siRNA and ASO targeting Pnky lncRNA to direct neuronal differentiation of NSCs.…”

“…Previously, we have successfully used intracellular delivery of the siRNA targeting Nogo-66 receptor (NgR) to direct neuronal differentiation of NSCs through silencing the NgR gene. 18 In the present study, we used siRNA and ASO targeting Pnky lncRNA to direct neuronal differentiation of NSCs. LncRNAs play key regulatory roles at virtually every level of cellular physiology, including cell differentiation.…”

Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy

“…NSC-based therapy is expected to offer unique therapeutic benefits to stroke, through differentiation into neurons to remedy damaged neurons and thereby reconstruct injured functional neural circuitry. , To our knowledge, this nanomedicine was the first one ever developed to direct neuronal stem cell differentiation via lncRNA downregulation. Previously, we have successfully used intracellular delivery of the siRNA targeting Nogo-66 receptor (NgR) to direct neuronal differentiation of NSCs through silencing the NgR gene . In the present study, we used siRNA and ASO targeting Pnky lncRNA to direct neuronal differentiation of NSCs.…”

“…Previously, we have successfully used intracellular delivery of the siRNA targeting Nogo-66 receptor (NgR) to direct neuronal differentiation of NSCs through silencing the NgR gene. 18 In the present study, we used siRNA and ASO targeting Pnky lncRNA to direct neuronal differentiation of NSCs. LncRNAs play key regulatory roles at virtually every level of cellular physiology, including cell differentiation.…”

Biocompatible Iron Oxide Nanoring-Labeled Mesenchymal Stem Cells: An Innovative Magnetothermal Approach for Cell Tracking and Targeted Stroke Therapy

“…The labeled GFP-MSCs, with cell numbers 10 3 and 10 5 , were transplanted into two groups of rats ( n = 6). MR images of the brain were acquired at weeks 1, 4, 8, and 10 for all groups, with the rats sacrificed following MRI measurement to harvest the tissues for histochemistry analysis . The T 2 * MR images of transplanted GFP-MSCs in the brain are presented in Figure b.…”

Ferrimagnetic Nanochains‐Based Mesenchymal Stem Cell Engineering for Highly Efficient Post‐Stroke Recovery

“…The high gene transfection efficiency of MFIONs without external magnetic force is beneficial for their potential clinical translation. Very recently, Lu et al reported a rationally well‐designed SPIONs‐based nanoscale polymersome to achieve highly efficient siRNA delivery into neural stem cells (NSCs) without the assistance of external magnetic field, which promoted the recovery of neural function in acute ischemic stroke . Herein, 1D nanostructured MFIONs with high aspect ratios are designed to facilitate the internalizations of their payload genes into MSCs.…”

Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy

“…NSC-based therapy is expected to offer unique therapeutic benefits to stroke, through differentiation into neurons to remedy damaged neurons and thereby reconstruct injured functional neural circuitry. , To our knowledge, this nanomedicine was the first one ever developed to direct neuronal stem cell differentiation via lncRNA downregulation. Previously, we have successfully used intracellular delivery of the siRNA targeting Nogo-66 receptor (NgR) to direct neuronal differentiation of NSCs through silencing the NgR gene . In the present study, we used siRNA and ASO targeting Pnky lncRNA to direct neuronal differentiation of NSCs.…”

“…Previously, we have successfully used intracellular delivery of the siRNA targeting Nogo-66 receptor (NgR) to direct neuronal differentiation of NSCs through silencing the NgR gene. 18 In the present study, we used siRNA and ASO targeting Pnky lncRNA to direct neuronal differentiation of NSCs. LncRNAs play key regulatory roles at virtually every level of cellular physiology, including cell differentiation.…”

Biocompatible Iron Oxide Nanoring-Labeled Mesenchymal Stem Cells: An Innovative Magnetothermal Approach for Cell Tracking and Targeted Stroke Therapy

“…The labeled GFP-MSCs, with cell numbers 10 3 and 10 5 , were transplanted into two groups of rats ( n = 6). MR images of the brain were acquired at weeks 1, 4, 8, and 10 for all groups, with the rats sacrificed following MRI measurement to harvest the tissues for histochemistry analysis . The T 2 * MR images of transplanted GFP-MSCs in the brain are presented in Figure b.…”

Ferrimagnetic Nanochains‐Based Mesenchymal Stem Cell Engineering for Highly Efficient Post‐Stroke Recovery

“…The high gene transfection efficiency of MFIONs without external magnetic force is beneficial for their potential clinical translation. Very recently, Lu et al reported a rationally well‐designed SPIONs‐based nanoscale polymersome to achieve highly efficient siRNA delivery into neural stem cells (NSCs) without the assistance of external magnetic field, which promoted the recovery of neural function in acute ischemic stroke . Herein, 1D nanostructured MFIONs with high aspect ratios are designed to facilitate the internalizations of their payload genes into MSCs.…”

Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy

“…NSC-based therapy is expected to offer unique therapeutic benefits to stroke, through differentiation into neurons to remedy damaged neurons and thereby reconstruct injured functional neural circuitry. , To our knowledge, this nanomedicine was the first one ever developed to direct neuronal stem cell differentiation via lncRNA downregulation. Previously, we have successfully used intracellular delivery of the siRNA targeting Nogo-66 receptor (NgR) to direct neuronal differentiation of NSCs through silencing the NgR gene . In the present study, we used siRNA and ASO targeting Pnky lncRNA to direct neuronal differentiation of NSCs.…”

“…Previously, we have successfully used intracellular delivery of the siRNA targeting Nogo-66 receptor (NgR) to direct neuronal differentiation of NSCs through silencing the NgR gene. 18 In the present study, we used siRNA and ASO targeting Pnky lncRNA to direct neuronal differentiation of NSCs. LncRNAs play key regulatory roles at virtually every level of cellular physiology, including cell differentiation.…”

Biocompatible Iron Oxide Nanoring-Labeled Mesenchymal Stem Cells: An Innovative Magnetothermal Approach for Cell Tracking and Targeted Stroke Therapy

“…The labeled GFP-MSCs, with cell numbers 10 3 and 10 5 , were transplanted into two groups of rats ( n = 6). MR images of the brain were acquired at weeks 1, 4, 8, and 10 for all groups, with the rats sacrificed following MRI measurement to harvest the tissues for histochemistry analysis . The T 2 * MR images of transplanted GFP-MSCs in the brain are presented in Figure b.…”

Ferrimagnetic Nanochains‐Based Mesenchymal Stem Cell Engineering for Highly Efficient Post‐Stroke Recovery

“…The high gene transfection efficiency of MFIONs without external magnetic force is beneficial for their potential clinical translation. Very recently, Lu et al reported a rationally well‐designed SPIONs‐based nanoscale polymersome to achieve highly efficient siRNA delivery into neural stem cells (NSCs) without the assistance of external magnetic field, which promoted the recovery of neural function in acute ischemic stroke . Herein, 1D nanostructured MFIONs with high aspect ratios are designed to facilitate the internalizations of their payload genes into MSCs.…”